伊利諾依大學(xué)芝加哥分校研究人員在12月9日出版的Cancer Cell上發(fā)表特刊文章,，講述氧化作用路徑與細(xì)胞衰老以及細(xì)胞凋亡間的關(guān)聯(lián)。
文章通訊作者Nissim Hay博士早年在以色列Weizmann研究所獲得博士學(xué)位,，現(xiàn)任伊利諾依大學(xué)芝加哥分校生物化學(xué)與分子遺傳學(xué)院任教授,，主要研究細(xì)胞分裂，細(xì)胞代謝和癌癥的遺傳學(xué)變化,，主要應(yīng)用的技術(shù)包括,，細(xì)胞生物學(xué)技術(shù)，生物化學(xué)技術(shù),，分子生物學(xué)技術(shù)和基因敲除技術(shù),。
Akt通路是膜受體信號向細(xì)胞內(nèi)轉(zhuǎn)導(dǎo)的重要途徑，它們調(diào)節(jié)著細(xì)胞凋亡,、生長以及一些重要基因的表達(dá),。
Akt缺陷會導(dǎo)致對衰老性復(fù)制產(chǎn)生耐受作用，對氧化應(yīng)激或致癌基因Ras誘導(dǎo)的早衰產(chǎn)生耐受作用,， 同時還對活性氧簇（reactive oxygen species,，ROS）介導(dǎo)的細(xì)胞凋亡產(chǎn)生耐受作用。
Akt活化可誘導(dǎo)早衰,，并通過增加胞內(nèi)ROS增加氧耗量和表達(dá)ROS清除下游FoxO尤其是sestrin致敏ROSE介導(dǎo)的細(xì)胞凋亡作用,。這些結(jié)果表明，研究者找到Akt的關(guān)鍵弱點(diǎn),，可以逆轉(zhuǎn)Akt通過多種細(xì)胞凋亡刺激因子誘導(dǎo)細(xì)胞凋亡的過程,。Akt可以停止抑制ROS介導(dǎo)的細(xì)胞凋亡。
研究小組還發(fā)現(xiàn),，用rapamycin治療癌癥可促進(jìn)激活A(yù)kt,，抑制etopototic超敏化，促進(jìn)癌細(xì)胞凋亡,。單獨(dú)使用rapamycin可有選擇性地激活A(yù)kt,，清除癌細(xì)胞。（生物谷Bioon.com）
生物谷推薦原始出處：
Cancer Cell, Volume 14, Issue 6, 458-470, 9 December 2008
Akt Determines Replicative Senescence and Oxidative or Oncogenic Premature Senescence and Sensitizes Cells to Oxidative Apoptosis
Veronique Nogueira1,Youngkyu Park1,Chia-Chen Chen1,Pei-Zhang Xu1,Mei-Ling Chen1,Ivana Tonic1,Terry Unterman2,3andNissim Hay1,,
1 Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, USA
2 Department of Medicine, University of Illinois at Chicago, Chicago, IL 60607, USA
3 Jesse Brown VA Medical Center, Chicago, IL 60612, USA
SUMMARY
Akt deficiency causes resistance to replicative senescence, to oxidative stress- and oncogenic Ras-induced premature senescence, and to reactive oxygen species (ROS)-mediated apoptosis. Akt activation induces premature senescence and sensitizes cells to ROS-mediated apoptosis by increasing intracellular ROS through increased oxygen consumption and by inhibiting the expression of ROS scavengers downstream of FoxO, particularly sestrin 3. This uncovers an Achilles' heel of Akt, since in contrast to its ability to inhibit apoptosis induced by multiple apoptotic stimuli, Akt could not inhibit ROS-mediated apoptosis. Furthermore, treatment with rapamycin that led to further Akt activation and resistance to etoposide hypersensitized cancer cells to ROS-mediated apoptosis. Given that rapamycin alone is mainly cytostatic, this constitutesa strategy for cancer therapy that selectively eradicates cancer cells via Akt activation.
